Editing Nerve agent (section)

===Countermeasures===
[[Pyridostigmine|Pyridostigmine bromide]] was used by the [[United States Armed Forces|US military]] in the [[Gulf War|first Gulf War]] as a pretreatment for [[Soman]] as it increased the [[median lethal dose]]. It is only effective if taken prior to exposure and in conjunction with Atropine and Pralidoxime, issued in the [[Mark I NAAK]] autoinjector, and is ineffective against other nerve agents. While it reduces fatality rates, there is an increased risk of brain damage; this can be mitigated by administration of an anticonvulsant.<ref>{{Cite web|date=2018-09-03|title=NERVE AGENTS|url=https://fas.org/nuke/guide/usa/doctrine/army/mmcch/NervAgnt.htm|access-date=2020-07-27|archive-url=https://web.archive.org/web/20180903235711/https://fas.org/nuke/guide/usa/doctrine/army/mmcch/NervAgnt.htm|archive-date=2018-09-03}}</ref> Evidence suggests that the use of pyridostigmine may be responsible for some of the symptoms of [[Gulf War syndrome]].<ref>{{Cite journal|last=Golomb|first=Beatrice Alexandra|date=2008-03-18|title=Acetylcholinesterase inhibitors and Gulf War illnesses|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=105|issue=11|pages=4295–4300|doi=10.1073/pnas.0711986105|issn=0027-8424|pmc=2393741|pmid=18332428|bibcode=2008PNAS..105.4295G|doi-access=free}}</ref>

[[Butyrylcholinesterase]] is under development by the U.S. Department of Defense as a [[prophylactic]] [[countermeasure]] against [[organophosphate]] nerve agents. It binds nerve agent in the bloodstream before the poison can exert effects in the nervous system.<ref name=pmid25448037>{{cite journal | vauthors = Lockridge O | title = Review of human butyrylcholinesterase structure, function, genetic variants, history of use in the clinic, and potential therapeutic uses | journal = Pharmacology & Therapeutics | volume = 148 | pages = 34–46 | date = April 2015 | pmid = 25448037 | doi = 10.1016/j.pharmthera.2014.11.011 }}</ref>

Both purified [[acetylcholinesterase]] and butyrylcholinesterase have demonstrated success in animal studies as "biological scavengers" (and universal targets) to provide [[stoichiometry|stoichiometric]] protection against the entire spectrum of organophosphate nerve agents.<ref name=pmid1986743>{{cite journal | vauthors = Ashani Y, Shapira S, Levy D, Wolfe AD, Doctor BP, Raveh L | title = Butyrylcholinesterase and acetylcholinesterase prophylaxis against Soman poisoning in mice | journal = Biochemical Pharmacology | volume = 41 | issue = 1 | pages = 37–41 | date = January 1991 | pmid = 1986743 | doi = 10.1016/0006-2952(91)90008-S }}</ref><ref name=pmid8343986>{{cite journal | vauthors = Doctor BP, Blick DW, Caranto G, Castro CA, Gentry MK, Larrison R, Maxwell DM, Murphy MR, Schutz M, Waibel K | title = Cholinesterases as scavengers for organophosphorus compounds: protection of primate performance against Soman toxicity | journal = Chemico-Biological Interactions | volume = 87 | issue = 1–3 | pages = 285–93 | date = June 1993 | pmid = 8343986 | doi = 10.1016/0009-2797(93)90056-5 | bibcode = 1993CBI....87..285D }}</ref> Butyrylcholinesterase currently is the preferred enzyme for development as a pharmaceutical drug primarily because it is a naturally circulating human plasma protein (superior [[pharmacokinetics]]) and its larger active site compared with acetylcholinesterase may permit greater flexibility for future design and improvement of butyrylcholinesterase to act as a nerve agent scavenger.<ref name=pmid10421478>{{cite journal | vauthors = Broomfield CA, Lockridge O, Millard CB | title = Protein engineering of a human enzyme that hydrolyzes V and G nerve agents: design, construction and characterization | journal = Chemico-Biological Interactions | volume = 119–120 | pages = 413–8 | date = May 1999 | pmid = 10421478 | doi = 10.1016/S0009-2797(99)00053-8 | bibcode = 1999CBI...119..413B }}</ref>